MAZ-mediated tumor progression and immune evasion in hormone receptor-positive breast cancer: Targeting tumor microenvironment and PCLAF+ subtype-specific therapy
Background: Breast cancer had been the most frequently diagnosed cancer among women, making up nearly one-third of all female cancers. Hormone receptor-positive breast cancer (HR+BC) was the most prevalent subtype of breast cancer and exhibited significant heterogeneity. Despite advancements in endo...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523325000117 |
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| author | Gaofeng Ni Yuwei Sun Hongling Jia Zhikai Xiahou Yumeng Li Fu Zhao Hongyan Zang |
| author_facet | Gaofeng Ni Yuwei Sun Hongling Jia Zhikai Xiahou Yumeng Li Fu Zhao Hongyan Zang |
| author_sort | Gaofeng Ni |
| collection | DOAJ |
| description | Background: Breast cancer had been the most frequently diagnosed cancer among women, making up nearly one-third of all female cancers. Hormone receptor-positive breast cancer (HR+BC) was the most prevalent subtype of breast cancer and exhibited significant heterogeneity. Despite advancements in endocrine therapies, patients with advanced HR+BC often faced poor outcomes due to the development of resistance to treatment. Understanding the molecular mechanisms behind this resistance, including tumor heterogeneity and changes in the tumor microenvironment, was crucial for overcoming resistance, identifying new therapeutic targets, and developing more effective personalized treatments. Methods: The study utilized single-cell RNA sequencing (scRNA-seq) data sourced from the Gene Expression Omnibus database and The Cancer Genome Atlas to analyze HR+BC and identify key cellular characteristics. Cell type identification was achieved through Seurat's analytical tools, and subtype differentiation trajectories were inferred using Slingshot. Cellular communication dynamics between tumor cell subtypes and other cells were analyzed with the CellChat. The pySCENIC package was utilized to analyze transcription factors regulatory networks in the identified tumor cell subtypes. The results were verified by in vitro experiments. A risk scoring model was developed to assess patient outcomes. Results: This study employed scRNA-seq to conduct a comprehensive analysis of HR+BC tumor subtypes, identifying the C3 PCLAF+ tumor cells subtype, which demonstrated high proliferation and differentiation potential. C3 PCLAF+ tumor cells subtype was found to be closely associated with cancer-associated fibroblasts through the MK signaling pathway, facilitating tumor progression. Additionally, we discovered that MAZ was significantly expressed in C3 PCLAF+ tumor cells subtype, and in vitro experiments confirmed that MAZ knockdown inhibited tumor growth, accentuating its underlying ability as a therapeutic target. Furthermore, we developed a novel prognostic model based on the expression profile of key prognostic genes within the PCLAF+/MAZ regulatory network. This model linked high PCLAF+ tumor risk scores with poor survival outcomes and specific immune microenvironment characteristics. Conclusion: This study utilized scRNA-seq to reveal the role of the C3 PCLAF+ tumor cells subtype in HR+BC, emphasizing its association with poor prognosis and resistance to endocrine therapies. MAZ, identified as a key regulator, contributed to tumor progression, while the tumor microenvironment had a pivotal identity in immune evasion. The findings underscored the importance of overcoming drug resistance, recognizing novel treatment targets, and crafting tailored diagnosis regimens. |
| format | Article |
| id | doaj-art-8193560873484cc1ab33b72adb391665 |
| institution | Kabale University |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-8193560873484cc1ab33b72adb3916652025-01-22T05:41:36ZengElsevierTranslational Oncology1936-52332025-02-0152102280MAZ-mediated tumor progression and immune evasion in hormone receptor-positive breast cancer: Targeting tumor microenvironment and PCLAF+ subtype-specific therapyGaofeng Ni0Yuwei Sun1Hongling Jia2Zhikai Xiahou3Yumeng Li4Fu Zhao5Hongyan Zang6Department of Breast Surgery, Yantaishan Hospital Affiliated to Binzhou Medical University, Yantai 264003, ChinaThe First Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan 250014, ChinaThe First Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan 250014, ChinaChina Institute of Sport and Health Science, Beijing Sport University, Beijing 100084, ChinaThe First Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan 250014, China; Corresponding authors.The First Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan 250014, China; Corresponding authors.Department of Breast Surgery, Yantaishan Hospital Affiliated to Binzhou Medical University, Yantai 264003, China; Corresponding authors.Background: Breast cancer had been the most frequently diagnosed cancer among women, making up nearly one-third of all female cancers. Hormone receptor-positive breast cancer (HR+BC) was the most prevalent subtype of breast cancer and exhibited significant heterogeneity. Despite advancements in endocrine therapies, patients with advanced HR+BC often faced poor outcomes due to the development of resistance to treatment. Understanding the molecular mechanisms behind this resistance, including tumor heterogeneity and changes in the tumor microenvironment, was crucial for overcoming resistance, identifying new therapeutic targets, and developing more effective personalized treatments. Methods: The study utilized single-cell RNA sequencing (scRNA-seq) data sourced from the Gene Expression Omnibus database and The Cancer Genome Atlas to analyze HR+BC and identify key cellular characteristics. Cell type identification was achieved through Seurat's analytical tools, and subtype differentiation trajectories were inferred using Slingshot. Cellular communication dynamics between tumor cell subtypes and other cells were analyzed with the CellChat. The pySCENIC package was utilized to analyze transcription factors regulatory networks in the identified tumor cell subtypes. The results were verified by in vitro experiments. A risk scoring model was developed to assess patient outcomes. Results: This study employed scRNA-seq to conduct a comprehensive analysis of HR+BC tumor subtypes, identifying the C3 PCLAF+ tumor cells subtype, which demonstrated high proliferation and differentiation potential. C3 PCLAF+ tumor cells subtype was found to be closely associated with cancer-associated fibroblasts through the MK signaling pathway, facilitating tumor progression. Additionally, we discovered that MAZ was significantly expressed in C3 PCLAF+ tumor cells subtype, and in vitro experiments confirmed that MAZ knockdown inhibited tumor growth, accentuating its underlying ability as a therapeutic target. Furthermore, we developed a novel prognostic model based on the expression profile of key prognostic genes within the PCLAF+/MAZ regulatory network. This model linked high PCLAF+ tumor risk scores with poor survival outcomes and specific immune microenvironment characteristics. Conclusion: This study utilized scRNA-seq to reveal the role of the C3 PCLAF+ tumor cells subtype in HR+BC, emphasizing its association with poor prognosis and resistance to endocrine therapies. MAZ, identified as a key regulator, contributed to tumor progression, while the tumor microenvironment had a pivotal identity in immune evasion. The findings underscored the importance of overcoming drug resistance, recognizing novel treatment targets, and crafting tailored diagnosis regimens.http://www.sciencedirect.com/science/article/pii/S1936523325000117Single-cell RNA sequencingHormone receptor-positive breast cancerTumor microenvironmentPrognosisImmunotherapy |
| spellingShingle | Gaofeng Ni Yuwei Sun Hongling Jia Zhikai Xiahou Yumeng Li Fu Zhao Hongyan Zang MAZ-mediated tumor progression and immune evasion in hormone receptor-positive breast cancer: Targeting tumor microenvironment and PCLAF+ subtype-specific therapy Translational Oncology Single-cell RNA sequencing Hormone receptor-positive breast cancer Tumor microenvironment Prognosis Immunotherapy |
| title | MAZ-mediated tumor progression and immune evasion in hormone receptor-positive breast cancer: Targeting tumor microenvironment and PCLAF+ subtype-specific therapy |
| title_full | MAZ-mediated tumor progression and immune evasion in hormone receptor-positive breast cancer: Targeting tumor microenvironment and PCLAF+ subtype-specific therapy |
| title_fullStr | MAZ-mediated tumor progression and immune evasion in hormone receptor-positive breast cancer: Targeting tumor microenvironment and PCLAF+ subtype-specific therapy |
| title_full_unstemmed | MAZ-mediated tumor progression and immune evasion in hormone receptor-positive breast cancer: Targeting tumor microenvironment and PCLAF+ subtype-specific therapy |
| title_short | MAZ-mediated tumor progression and immune evasion in hormone receptor-positive breast cancer: Targeting tumor microenvironment and PCLAF+ subtype-specific therapy |
| title_sort | maz mediated tumor progression and immune evasion in hormone receptor positive breast cancer targeting tumor microenvironment and pclaf subtype specific therapy |
| topic | Single-cell RNA sequencing Hormone receptor-positive breast cancer Tumor microenvironment Prognosis Immunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S1936523325000117 |
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